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1.
Pharm Biol ; 61(1): 1401-1412, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37667488

RESUMEN

CONTEXT: Panax japonicus is the dried rhizome of Panax japonicus C.A. Mey. (Araliaceae). Saponins from Panax japonicus (SPJ) exhibit anti-oxidative and anti-aging effects. OBJECTIVE: We evaluated the neuroprotective effects of SPJ on aging rats. MATERIALS AND METHODS: Sprague-Dawley rats (18-months-old) were randomly divided into aging and SPJ groups (n = 8). Five-month-old rats were taken as the adult control (n = 8). The rats were fed a normal chow diet or the SPJ-containing diet (10 or 30 mg/kg) for 4 months. An in vitro model was established by d-galactose (d-Gal) in the SH-SY5Y cell line and pretreated with SPJ (25 and 50 µg/mL). The neuroprotection of SPJ was evaluated via Nissl staining, flow cytometry, transmission electron microscopy and Western blotting in vivo and in vitro. RESULTS: SPJ improved the neuronal degeneration and mitochondrial morphology that are associated with aging. Meanwhile, SPJ up-regulated the protein levels of mitofusin 2 (Mfn2) and optic atrophy 1 (Opa1) and down-regulated the protein level of dynamin-like protein 1 (Drp1) in the hippocampus of aging rats (p < 0.05 or p < 0.01 vs. 22 M). The in vitro studies also demonstrated that SPJ attenuated d-Gal-induced cell senescence concomitant with the improvement in mitochondrial function; SPJ, also up-regulated the Mfn2 and Opa1 protein levels, whereas the Drp1 protein level (p < 0.05 or p < 0.01 vs. d-Gal group) was down-regulated. DISCUSSION AND CONCLUSIONS: Further research on the elderly population will contribute to the development and utilization of SPJ for the treatment of neurodegenerative disorders.


Asunto(s)
Neuroblastoma , Panax , Anciano , Humanos , Ratas , Animales , Ratas Sprague-Dawley , Envejecimiento , Galactosa , Mitocondrias
2.
Ying Yong Sheng Tai Xue Bao ; 33(3): 749-756, 2022 Mar.
Artículo en Chino | MEDLINE | ID: mdl-35524528

RESUMEN

In Taiyue Mountain of Shanxi Province, five types of organic matter, i.e., biochar, maize straw, leaves of Quercus mongolica and Pinus tabuliformis, and sawdust of wood stem, were separately added to the soils of a P. tabuliformis forest. Nutrient content, enzyme activity, and microbial biomass were analyzed to elucidate the characteristics of soil ecoenzymatic stoichiometry and the element homeostasis of soil microorganisms. The results showed that the addition of woody sawdust significantly increased soil nitrogen and phosphorus content by 17.1% and 37.6%, and enhanced carbon, nitrogen, and phosphorus contents of soil microbial biomass by 118.0%, 41.0%, and 176.6%, respectively. The activities of carbon-, nitrogen- and phosphorus-targeting enzymes (i.e., ß-1, 4-glucosaminosidase, ß-1,4-N-acetylglucosaminosidase, leucine aminopeptidase and acid phosphatase) generally increased with the C:N of the added organic matter (biochar

Asunto(s)
Pinus , Suelo , Biomasa , Carbono/análisis , China , Bosques , Homeostasis , Nitrógeno/análisis , Fósforo/análisis , Microbiología del Suelo , Zea mays
3.
Zhongguo Zhong Yao Za Zhi ; 46(19): 5064-5071, 2021 Oct.
Artículo en Chino | MEDLINE | ID: mdl-34738402

RESUMEN

The present study investigated the effects of chikusetsu saponin Ⅳa(CHS Ⅳa) on isoproterenol(ISO)-induced myocardial hypertrophy in rats and explored the underlying molecular mechanism. ISO was applied to establish a rat model of myocardial hypertrophy, and CHS Ⅳa(5 and 15 mg·kg~(-1)·d~(-1)) was used for intervention. The tail artery blood pressure was measured. Cardiac ultrasound examination was performed. The ratio of heart weight to body weight(HW/BW) was calculated. Morphological changes in the myocardial tissue were observed by HE staining. Collagen deposition in the myocardial tissue was observed by Masson staining. The mRNA expression of myocardial hypertrophy indicators(ANP and BNP), autophagy-related genes(Atg5, P62 and beclin1), and miR199 a-5 p was detected by qRT-PCR. Atg5 protein expression was detected by Western blot. The results showed that the model group exhibited increased tail artery blood pressure and HW/BW ratio, thickened left ventricular myocardium, enlarged myocardial cells, disordered myocardial fibers with widened interstitium, and a large amount of collagen aggregating around the extracellular matrix and blood vessels. ANP and BNP were largely expressed. Moreover, P62 expression was up-regulated, while beclin1 expression was down-regulated. After intervention by CHS Ⅳa at different doses, myocardial hypertrophy was ameliorated and autophagy activity in the myocardial tissue was enhanced. Meanwhile, miR199 a-5 p expression declined and Atg5 expression increased. As predicted by bioinformatics, Atg5 was a target gene of miR199 a-5 p. CHS Ⅳa was capable of preventing myocardial hypertrophy by regulating autophagy of myocardial cells through the miR-199 a-5 p/Atg5 signaling pathway.


Asunto(s)
Ácido Oleanólico , Saponinas , Animales , Cardiomegalia/inducido químicamente , Cardiomegalia/tratamiento farmacológico , Cardiomegalia/genética , Isoproterenol , Miocardio , Miocitos Cardíacos , Ácido Oleanólico/análogos & derivados , Ratas , Saponinas/farmacología
4.
Pharm Biol ; 59(1): 1117-1125, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34403300

RESUMEN

CONTEXT: Panax japonicus is the dried rhizome of Panax japonicus C.A. Mey. (Araliaceae). Saponins from Panax japonicus (SPJ) exhibit anti-inflammatory and antioxidative effects. OBJECTIVE: To explore the neuroprotective effect of SPJ on natural ageing of rat. MATERIALS AND METHODS: Sprague-Dawley (SD) rats 18-month-old were divided into ageing control, ageing treated with SPJ 10 or 30 mg/kg (n = 8). Five-month-old rats were taken as the adult control (n = 8). Rats were fed regular feed or feed containing SPJ for 4 months. Cognitive level was evaluated by Morris water maze (MWM) test. The mechanisms of SPJ's neuroprotection were evaluated by transmission electron microscope, western blot analysis, and immunofluorescence in vivo and in vitro. RESULTS: SPJ attenuated ageing-induced cognitive impairment as indicated by elevated number of times crossing the target platform (from 1.63 to 3.5) and longer time spent in the target platform quadrant (from 1.33 to 1.98). Meanwhile, SPJ improved the morphology of microglia and synapse, and activated M2 microglia polarisation including increased hippocampus levels of CD206 (from 0.98 to 1.47) and YM-1 (from 0.67 to 1.1), and enhanced autophagy-related proteins LC3B (from 0.48 to 0.82), Beclin1 (from 0.32 to 0.51), Atg5 (from 0.22 to 0.89) whereas decreased p62 level (from 0.71 to 0.45) of ageing rats. In vitro study also showed that SPJ regulated the microglial polarisation and autophagy. DISCUSSION AND CONCLUSIONS: SPJ improved cognitive deficits of ageing rats through attenuating microglial inflammation and enhancing microglial autophagy, which could be used to treat neurodegenerative disorders.


Asunto(s)
Microglía/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Panax/química , Saponinas/farmacología , Envejecimiento , Animales , Autofagia/efectos de los fármacos , Disfunción Cognitiva/tratamiento farmacológico , Hipocampo/efectos de los fármacos , Inflamación/tratamiento farmacológico , Inflamación/patología , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Fármacos Neuroprotectores/aislamiento & purificación , Ratas , Ratas Sprague-Dawley , Saponinas/aislamiento & purificación
5.
J Pediatr Surg ; 56(10): 1711-1717, 2021 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-34120738

RESUMEN

OBJECTIVE: To develop a mathematical model based on a combination of clinical and radiologic features (barium enema) for early diagnosis of short-segment Hirschsprung disease (SHSCR) in neonate. METHODS: The analysis included 54 neonates with biopsy-confirmed SHSCR (the cases) and 59 neonates undergoing barium enema for abdominal symptoms but no Hirschsprung disease (the control). Colon shape features extracted from barium enema images and clinical features were used to develop diagnostic models using support vector machine (SVM) and L2-regularized logistic regression (LR). The training cohort included 32 cases and 37 controls; testing cohort consisted 22 cases and 22 controls. Results were compared to interpretation by 2 radiologists. RESULTS: In the analysis by radiologists, 87 out of 113 cases were correctly classified. Six SHSCR cases were mis-classified into the non-HSCR group. In the remaining 20 cases, radiologists were unable to make a decision. Both the SVM and LR classifiers contained five clinical features and four shape features. The performance of the two classifiers was similar. The best model had 86.36% accuracy, 81.82% sensitivity, and 90.91% specificity. The AUC was 0.9132 for the best-performing SVM classifier and 0.9318 for the best-performing LR classifier. CONCLUSION: A combination of clinical features and colon shape features extracted from barium enemas can be used to improve early diagnosis of SHSCR in neonate.


Asunto(s)
Enema Opaco , Enfermedad de Hirschsprung , Sulfato de Bario , Diagnóstico Precoz , Enema , Enfermedad de Hirschsprung/diagnóstico por imagen , Humanos , Recién Nacido , Aprendizaje Automático
6.
Curr Pharm Biotechnol ; 21(8): 667-680, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-31840608

RESUMEN

BACKGROUND: Oxidative stress and mitochondrial dysfunction play a vital role in the pathogenesis of brain aging. Saponins from Panax japonicus (SPJ) have attracted much attention for their potential to attenuate age-related oxidative stress as the main ingredient in rhizomes of Panax japonicus. OBJECTIVE: This study aimed to investigate the neuroprotective effects of SPJ on natural aging rats as well as the underlying mechanisms regarding oxidative stress and mitochondrial pathway. METHODS: Sprague-Dawley rats were divided into control groups (3-, 9-, 15- and 24-month old groups) and SPJ-treated groups. For SPJ-treated groups, SPJ were orally administrated to 18-month old rats at doses of 10 mg/kg, 30 mg/kg and 60 mg/kg once daily. Control groups were given the same volume of saline. After the treatment with SPJ or saline for six months, the cortex and hippocampus were rapidly harvested and deposited at -80°C after the rats were decapitated under anesthesia. The neuroprotective effects of SPJ were estimated by histopathological observation, TUNEL detection, biochemical determination and western blotting. RESULTS: SPJ improved pathomorphological changes in neuronal cells and decreased apoptosis in the cortex and hippocampus of aging rats, increased the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), Na+/K+-ATPase, Ca2+-ATPase and Ca2+/Mg2+-ATPase whereas, decreased malondialdehyde (MDA) contents in the cortex of aging rats. Furthermore, the SPJ increased silent mating type information regulation 2 homolog-1 (SIRT1) protein expression, decreased acetylated level of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) in the cortex and hippocampus of aging rats, and reversed the aging-induced decline of Forkhead box O3 (Foxo3a), Superoxide Dismutase 2 (SOD2), microtubule-associated protein light chain 3 (LC3II) and Beclin1 levels in the cortex and hippocampus. CONCLUSION: Our data showed that SPJ conferred neuroprotection partly through the regulation of oxidative stress and mitochondria-related pathways in aging rats.


Asunto(s)
Envejecimiento/efectos de los fármacos , Autofagia/efectos de los fármacos , Encéfalo/efectos de los fármacos , Mitocondrias/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Estrés Oxidativo/efectos de los fármacos , Panax/química , Saponinas/farmacología , Envejecimiento/metabolismo , Envejecimiento/patología , Animales , Apoptosis/efectos de los fármacos , Encéfalo/metabolismo , Encéfalo/patología , Masculino , Malondialdehído/metabolismo , Mitocondrias/metabolismo , Mitocondrias/patología , Fármacos Neuroprotectores/aislamiento & purificación , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/metabolismo , Ratas , Ratas Sprague-Dawley , Saponinas/aislamiento & purificación , Sirtuina 1/metabolismo , Superóxido Dismutasa/metabolismo
7.
Zhongguo Zhong Yao Za Zhi ; 44(2): 344-349, 2019 Jan.
Artículo en Chino | MEDLINE | ID: mdl-30989956

RESUMEN

The aim of this paper was to investigate the effect of total saponins from Panax japonicus( SPJ) on cognitive decline of natural aging rats and its mechanism. Thirty male SD rats of eighteen month old were randomly divided into three groups: aged group,10 mg·kg~(-1) SPJ-treated group and 30 mg·kg~(-1) SPJ-treated group. The SPJ-treated groups were given SPJ at the dosages of 10 mg·kg~(-1) and 30 mg·kg~(-1),respectively,from the age of 18 to 24 months. Aged group were lavaged the same amount of saline,10 six-month-old rats were used as control group,with 10 rats in each group. The open field test,novel object recognition and Morris water maze were performed to detect the changes of cognitive function in each group. The changes of synaptic transmission of long-term potentiation( LTP) in hippocampal CA1 region were detected by field potential recording. Western blot was used to detect the protein levels of NLRP3,ASC,caspase-1 and the changes of Glu A1,Glu A2,CAMKⅡ,CREB and phosphorylation of CAMKⅡ,CREB in each group.The results showed that SPJ could improve the decline of cognitive function in aging rats,reduce the damage of LTP in the hippocampal CA1 region of aged rats,and decrease the expression of NLRP3,ASC,caspase-1 in aging rats. At the same time,SPJ could enhance the membrane expression of AMPA receptor( Glu A1 and Glu A2),and increase the expression of p-CAMKⅡand p-CREB in aging rats.SPJ could improve cognitive decline of natural aging rats,and its mechanism may be related to regulating NLRP3 inflammasome,thus regulating the membrane expression of AMPA receptor,and enhancing the expression phosphorylation of CAMKⅡ and CREB.


Asunto(s)
Envejecimiento , Cognición/efectos de los fármacos , Inflamasomas/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Panax/química , Saponinas/farmacología , Animales , Región CA1 Hipocampal/fisiología , Potenciación a Largo Plazo , Masculino , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley
8.
Zhongguo Zhong Yao Za Zhi ; 43(22): 4513-4518, 2018 Nov.
Artículo en Chino | MEDLINE | ID: mdl-30593247

RESUMEN

To investigate the amelioration effect of saponins extracted from Panax japonicas (SPJ) on myocardial fibrosis in natural aging rats and its mechanisms, male SD rats aged 18 months were randomly divided into 3 groups (aging model group, low-dose SPJ group and high-dose SPJ group), with 10 rats in each group. SPJ groups were given SPJ at different doses (10, 60 mg·kg⁻¹·d⁻¹) consecutively for 6 months, meanwhile, aging model group was treated with the equal volume of saline for 6 months until 24 months old. Another 10 rats aged 6 month were used as young control group. The changes of myocardial morphological were observed by haematoxylin-eosin (HE) staining. Masson staining was used to observe the changes of collagen deposition in rat hearts. RT-PCR was used to detect the mRNA expression levels of myofibroblast marker α-SMA, collagen-related protein COL1α2, COL3α1 and matrix metalloproteinase MMP2, MMP9. Western blot was used to test the changes of the protein expressions of TGF-ß1, p-Smad3, IL-1ß and TNF-α in heart tissues. SPJ can effectively improve the arrangement of myocardial fibers, decrease inflammatory infiltration and reduce collagen deposition in aging rats. SPJ can effectively down-regulate the mRNA expression levels of COL1α2, COL3α1, α-SMA, MMP9, MMP2 and inhibit the protein expressions of TGF-ß1, p-Smad3, TNF-α, IL-1ß in the natural aging heart tissues. SPJ can effectively alleviate myocardial fibrosis in natural aging rats, and its mechanisms was related to the inhibition of the protein expressions of TGF-ß1, p-Smad3 and the reduction of myocardial inflammation in rat hearts.


Asunto(s)
Panax , Animales , Fibrosis , Masculino , Ratas , Ratas Sprague-Dawley , Saponinas , Transducción de Señal , Proteína smad3 , Factor de Crecimiento Transformador beta1
9.
Zhongguo Zhong Yao Za Zhi ; 42(3): 555-561, 2017 Feb.
Artículo en Chino | MEDLINE | ID: mdl-28952264

RESUMEN

To investigate the protective effect of Panax notoginseng saponins combined with total flavonoids of epimedium on D-gal-induced senescence of H9c2 cells and explore its underlying mechanisms. The 50 mol•L⁻¹ D-gal was used to induce H9c2 cells senescence. Different concentrations of TPNS, TFE, and TPNS combined with TFE were used for 4 hours for pre-treatment. D-gal was used to stimulate H9c2 cardiac muscle cells for 24 h. Then in order to determine the best combined scheme, MTT was used to detect cell viability. Cell senescence was identified by ß-galactosidase staining. Levels of reactive oxygen species(ROS) was observed by DCFH-DA detection. The changes of mitochondrial membrane potential were identified by JC-1 detection. Protein levels of silentmating type information regulation 2 Homolog-1(SIRT1), peroxisomal proliferator-activated receptor-coactivator 1α(PGC-1α) and silentmating type information regulation 2 Homolog-3(SIRT3) were detected by western blot analysis. The results showed that TPNS(5 mg•L⁻¹) combined with TFE(5 mg•L⁻¹) had significant synergistic effect on H9c2 myocardial cell proliferation(Q=1.154), so 5 mg•L-1TPNS combined with 5 mg•L⁻¹ TFE was determined as the best scheme. The quantity of ß-galactosidase staining and the fluorescence intensity of ROS were apparently decreased in 5 mg•L⁻¹ TPNS combined with 5 mg•L⁻¹ TFE scheme. Meanwhile, it markedly increased the florescence intensity of mitochondrial membrane potential and enhanced the protein expression of SIRT1, PGC-1α and SIRT3. TPNS combined with TFE could protect H9c2 cells from D-gal-induced senescence. The mechanism might be related to adjusting the signal pathways of SIRT1/PGC-1α, SIRT3, adjusting the structure and function of mitochondria and reducing oxidative stress injury.


Asunto(s)
Epimedium/química , Flavonoides/farmacología , Panax notoginseng/química , Saponinas/farmacología , Animales , Línea Celular , Galactosa , Ratas , Transducción de Señal
10.
Zhongguo Zhong Yao Za Zhi ; 42(23): 4656-4660, 2017 Dec.
Artículo en Chino | MEDLINE | ID: mdl-29376267

RESUMEN

To investigate the effects of saponins extracted from Panax japonicus(SPJ) on cardiomyocyte apoptosis in natural aging rats and explore its underlying mechanisms. SD male rats were randomly divided into four groups: young control group, natural aging group, SPJ low dose group and SPJ high dose group, with 10 rats in each group. The rats in natural aging group, SPJ low and high dose groups were respectively treated with normal saline, SPJ 10 and 60 mg•kg-1•d-1 from the beginning of 18 month-old, 6 days per week for 6 months till 24 month-old. Then the animals were sacrificed. Their myocardial morphology changes were observed by using haematoxylin-eoin(HE) staining; cardiomyocyte apoptosis was tested by using Tunel assays; and the protein expression levels of Bcl-2, Bax, IL-1ß, TNF-α, AMPK, p-AMPK, Sirt1, and Ac-NF-κB p65 in myocardial tissues of rats were detected by Western blot. The results showed that SPJ could effectively improve the arrangement disorder of myocardial fibers, reduce the infiltration of inflammatory cells and inhibit cardiomyocyte apoptosis in natural aging rats. At the same time, SPJ could significantly inhibit the protein expression of Bax, IL-1ß, TNF-α and Ac-NF-κB p65, and increase the expression of Bcl-2, Bcl-2/Bax, p-AMPK/AMPK and Sirt1 in the heart tissues of natural aging rats. SPJ can effectively inhibit cardiomyocyte apoptosis in natural aging rats, and its mechanisms may be related with the regulation of inflammatory reaction by AMPK/Sirt1/NF-κB signaling pathway.


Asunto(s)
Envejecimiento , Apoptosis , Miocitos Cardíacos/efectos de los fármacos , Panax/química , Saponinas/farmacología , Transducción de Señal , Adenilato Quinasa/metabolismo , Animales , Masculino , Miocitos Cardíacos/citología , FN-kappa B/metabolismo , Ratas , Ratas Sprague-Dawley , Sirtuina 1/metabolismo
11.
Immunopharmacol Immunotoxicol ; 38(3): 167-74, 2016 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-26981791

RESUMEN

Chikusetsusaponin V (CsV), a saponin from Panax japonicus, has been reported to inhibit inflammatory responses in lipopolysaccharide (LPS)-induced macrophage cells. However, whether CsV could alleviate LPS-induced liver injury in vivo and the potential mechanisms involved remain unclear. In the present study, we investigated the anti-inflammatory effects of CsV on LPS-induced acute liver injury in mice and further explored the potential mechanisms involved. Our results showed that CsV significantly attenuated elevation of alanine transaminase (ALT) and aspartate aminotransferase (AST) levels and improved liver histopathological changes in LPS-induced mice. In addition, CsV decreased serum tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) levels and inhibited mRNA expressions of inducible nitric oxide synthase (iNOS), TNF-α and IL-1ß in LPS challenged mice. Furthermore, CsV inhibited nuclear factor kappa B (NF-κB) activation by downregulating phosphorylated NF-κB, IκB-α, ERK, c-Jun N-terminal kinase (JNK) and p38 levels in the liver tissue, which ultimately decreased nucleus NF-κB protein level. In conclusion, our data suggested that CsV could be a promising drug for preventing LPS challenged liver injury since it attenuated LPS-induced inflammatory responses, partly via inhibiting NF-κB and MAPK signaling pathways.


Asunto(s)
Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Lipopolisacáridos/toxicidad , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Saponinas/farmacología , Animales , Enfermedad Hepática Inducida por Sustancias y Drogas/inmunología , Interleucina-1beta/inmunología , MAP Quinasa Quinasa 4/inmunología , Sistema de Señalización de MAP Quinasas/inmunología , Masculino , Ratones , Ratones Endogámicos BALB C , FN-kappa B/inmunología , Panax/química , Saponinas/química , Factor de Necrosis Tumoral alfa/inmunología , Proteínas Quinasas p38 Activadas por Mitógenos/inmunología
12.
Molecules ; 19(5): 5748-60, 2014 May 05.
Artículo en Inglés | MEDLINE | ID: mdl-24802986

RESUMEN

Inhibition of cytochrome P450 (CYP) and P-glycoprotein (P-gp) are regarded as the most frequent and clinically important pharmacokinetic causes among the various possible factors for drug-drug interactions. Scutellarin is a flavonoid which is widely used for the treatment of cardiovascular diseases. In this study, the in vitro inhibitory effects of scutellarin on six major human CYPs (CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP3A4) and six rat CYPs (CYP1A2, CYP2C7, CYP2C11, CYP2C79, CYP2D4, and CYP3A2) activities were examined by using liquid chromatography-tandem mass spectrometry. Meanwhile, the inhibitory effects of scutellarin on P-gp activity were examined on a human metastatic malignant melanoma cell line WM-266-4 by calcein-AM fluorometry screening assay. Results demonstrated that scutellarin showed negligible inhibitory effects on the six major CYP isoenzymes in human/rat liver microsomes with almost all of the IC50 values exceeding 100 µM, whereas it showed values of 63.8 µM for CYP2C19 in human liver microsomes, and 63.1 and 85.6 µM for CYP2C7 and CYP2C79 in rat liver microsomes, respectively. Scutellarin also showed weak inhibitory effect on P-gp. In conclusion, this study demonstrates that scutellarin is unlikely to cause any clinically significant herb-drug interactions in humans when co-administered with substrates of the six CYPs (CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP3A4) and P-gp.


Asunto(s)
Apigenina/administración & dosificación , Inhibidores Enzimáticos del Citocromo P-450/administración & dosificación , Sistema Enzimático del Citocromo P-450/biosíntesis , Regulación Enzimológica de la Expresión Génica/efectos de los fármacos , Glucuronatos/administración & dosificación , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/biosíntesis , Animales , Hidrocarburo de Aril Hidroxilasas/biosíntesis , Citocromo P-450 CYP1A2/biosíntesis , Citocromo P-450 CYP2D6/biosíntesis , Citocromo P-450 CYP3A/biosíntesis , Sistema Enzimático del Citocromo P-450/genética , Familia 2 del Citocromo P450 , Humanos , Ratas , Esteroide 16-alfa-Hidroxilasa/biosíntesis
13.
J Ethnopharmacol ; 139(1): 104-9, 2012 Jan 06.
Artículo en Inglés | MEDLINE | ID: mdl-22079696

RESUMEN

ETHNOPHARMACOLOGICAL RELEVANCE: Herba Erigerontis injection (HEI), one of the most popular herbal prescription in China, is made from the aqueous extracts of Erigeron breviscapus whole plant. Now HEI is widely used for the treatment of cardiovascular diseases and cerebrovascular diseases such as coronary heart disease, anginapectoris and paralysis. AIM OF THE STUDY: The purpose of this study was to investigate the in vivo effect of HEI on rat cytochrome P450 enzymes (CYP1A2, CYP2C11, CYP2D4, CYP2E1 and CYP3A2) to assess its safety through its potential to interact with co-administered drugs. MATERIALS AND METHODS: Rats were randomly divided into five groups. Rats were intravenous administrated with HEI via the caudal vein at the dosage of 1.8ml/kg or 7.2ml/kg once daily for consecutive 3 days or 14 days. On the fourth or the fifteenth day, a cocktail solution at a dose of 5ml/kg, which contained caffeine (2.5mg/kg), tolbutamide (2.5mg/kg), chlorzoxazone (5mg/kg), midazolam (5mg/kg) and metoprolol (10mg/kg), was injected via the lingual vein to all rats. Then 0.8ml blood samples were collected at a set of time-points. The plasma concentrations of probe drugs were simultaneously determined by HPLC. Pharmacokinetic parameters simulated by DAS software were used for the evaluation of HEI on the activities of rat CYP1A2, CYP2C11, CYP2D4, CYP2E1 and CYP3A2 enzymes. ANOVA and Dunnett's test was used for data analysis. RESULTS: There were no significant influence of pharmacokinetic parameters of caffeine, tolbutamide and chlorzoxazone in HEI pretreated rats. But many pharmacokinetic parameters of metoprolol and midazolam in HEI pretreated rats were affected significantly (P<0.05), which indicated that metabolism of metoprolol and midazolam in these treatment groups was evidently slowed down. CONCLUSIONS: The results from the present in vivo study suggested that HEI showed no effects on rat CYP1A2, CYP2C11 and CYP2E1, however, it demonstrated potential inhibitory effects on rat CYP2D4 and CYP3A2. Therefore, caution is needed when HEI is co-administered with drugs metabolized by human CYP2D6 or CYP3A4 in clinic, which may result in increased concentrations of these drugs and relevant herb-drug interactions.


Asunto(s)
Sistema Enzimático del Citocromo P-450/metabolismo , Medicamentos Herbarios Chinos/farmacología , Inhibidores Enzimáticos/farmacología , Erigeron , Interacciones de Hierba-Droga , Animales , Área Bajo la Curva , Cafeína/sangre , Cafeína/farmacocinética , Clorzoxazona/sangre , Clorzoxazona/farmacocinética , Inhibidores Enzimáticos del Citocromo P-450 , Metoprolol/sangre , Metoprolol/farmacocinética , Midazolam/sangre , Midazolam/farmacocinética , Ratas , Ratas Sprague-Dawley , Tolbutamida/sangre , Tolbutamida/farmacocinética
14.
Phytother Res ; 25(11): 1660-5, 2011 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-21425377

RESUMEN

Huanglian (Rhizoma Coptidis) as a popular herb has been used for the treatment of various diseases such as diarrhea, eye inflammation and women's abdominal ailments. Alkaloids are considered to be responsible for its pharmacological effects. In this investigation, Huanglian and its six alkaloids (coptisine, epiberberine, berberine, jateorrhizine, palmatine and magnoflorine) were systematically evaluated for their inhibition of six cytochrome P450 isoforms (CYP1A2, CYP2C8, CYP2C9, CYP2C19, CYP2D6 and CYP3A4) in human liver microsomes by the LC-MS/MS method. Huanglian showed the strongest inhibition of CYP2D6, followed by CYP1A2 and CYP3A4_T. The IC50 values were 5.8 µg/mL, 36.8 µg/mL and 59.2 µg/mL, respectively. Of the constituents tested, coptisine and epiberberine showed strong inhibition of CYP2D6 with IC50 values of 4.4 µM and 7.7 µM; berberine, jateorrhizine and palmatine showed weak inhibition of CYP2D6 with IC50 values of 45.5 µM, 49.4 µM and 92.6 µM, respectively; jateorrhizine showed moderate inhibition of CYP3A4_T with an IC50 value of 13.3 µM; coptisine showed weak inhibition of CYP1A2 with an IC50 value of 37.3 µM. In addition, activation was observed in coptisine/CYP2C9 and palmatine/CYP2C9/CYP2C19. Other CYP450 isoforms were not affected markedly by the six alkaloids. In conclusion, Huanglian showed in vitro inhibition of CYP2D6, the inhibition might be contributed mostly by protoberberine alkaloids, especially coptisine and epiberberine. Herb-drug interactions may occur through the CYP2D6 inhibition.


Asunto(s)
Alcaloides/farmacología , Coptis/química , Sistema Enzimático del Citocromo P-450/efectos de los fármacos , Medicamentos Herbarios Chinos/farmacología , Microsomas Hepáticos/efectos de los fármacos , Interacciones de Hierba-Droga , Humanos , Concentración 50 Inhibidora , Isoenzimas/efectos de los fármacos , Rizoma/química
15.
Zhonghua Yi Shi Za Zhi ; 39(6): 353-6, 2009 Nov.
Artículo en Chino | MEDLINE | ID: mdl-20193445

RESUMEN

Since Speed first treated the radial head fracture with a metal prosthesis in 1941, the purpose of the treatment of radial head fracture with a radial head changed from the prevention of heterotopic ossification to the prevention of proximal migration of the radius and instability of the elbow. The optimal indication is gradually determined as a non-reconstructable radial head fracture with associated injuries that would leave the elbow unstable if the radial head were resected. Types of prosthesis changed from mono-block, bipolar to modular prosthesis. Material of prosthesis changed from acrylic resin, silastic to cobalt-chrome titanium and pyrocarbon. The 60-year development indicated that the operative technology of radial head prostheses was to be improved so as to reconstruct the flexibility and stability of the elbow to meet the higher functional requirements of patents.


Asunto(s)
Diseño de Prótesis , Fracturas del Radio , Articulación del Codo , Humanos
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